Is flow velocity a significant parameter in flood damage modelling?

Flow velocity is generally presumed to influence flood damage. However, this influence is hardly quantified and virtually no damage models take it into account. Therefore, the influences of flow velocity, water depth and combinations of these two impact parameters on various types of flood damage were investigated in five communities affected by the Elbe catchment flood in Germany in 2002. 2-D hydraulic models with high to medium spatial resolutions were used to calculate the impact parameters at the sites in which damage occurred. A significant influence of flow velocity on structural damage, particularly on roads, could be shown in contrast to a minor influence on monetary losses and business interruption. Forecasts of structural damage to road infrastructure should be based on flow velocity alone. The energy head is suggested as a suitable flood impact parameter for reliable forecasting of structural damage to residential buildings above a critical impact level of 2 m of energy head or water depth. However, general consideration of flow velocity in flood damage modelling, particularly for estimating monetary loss, cannot be recommended

Is flow velocity a significant parameter in flood damage modelling?

Flow velocity is generally presumed to influence flood damage. However, this influence is hardly quantified and virtually no damage models take it into account. Therefore, the influences of flow velocity, water depth and combinations of these two impact parameters on various types of flood damage were investigated in five communities affected by the Elbe catchment flood in Germany in 2002. 2-D hydraulic models with high to medium spatial resolutions were used to calculate the impact parameters at the sites in which damage occurred. A significant influence of flow velocity on structural damage, particularly on roads, could be shown in contrast to a minor influence on monetary losses and business interruption. Forecasts of structural damage to road infrastructure should be based on flow velocity alone. The energy head is suggested as a suitable flood impact parameter for reliable forecasting of structural damage to residential buildings above a critical impact level of 2m of energy head or water depth. However, general consideration of flow velocity in flood damage modelling, particularly for estimating monetary loss, cannot be recommended

Use of Surrogate end points in HTA

The different actors involved in health system decision-making and regulation have to deal with the question which are valid parameters to assess the health value of health technologies

Viraneler

Ercüment Ekrem'in Dersaadet ve Diken'de tefrika edilen Viraneler adlı romanıDersaadet'te tefrika edilirken süreli yayın kapandığından tefrika yarım kalmıştır. Devamı Diken gazetesinde yayımlanmıştır.Diken'de tefrika edilirken roman yarım kalmıştır. Kopuk adıyla İleri gazetesinde tefrika edilmiştir.Telif hakları nedeniyle romanın tam metni verilememiştir

Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease

Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials

Gaining Greater Insight into HCV Emergence in HIV-Infected Men Who Have Sex with Men: The HEPAIG Study

OBJECTIVES: The HEPAIG study was conducted to better understand Hepatitis C virus (HCV) transmission among human immuno-deficiency (HIV)-infected men who have sex with men (MSM) and assess incidence of HCV infection among this population in France. METHODS AND RESULTS: Acute HCV infection defined by anti-HCV or HCV ribonucleic acid (RNA) positivity within one year of documented anti-HCV negativity was notified among HIV-infected MSM followed up in HIV/AIDS clinics from a nationwide sampling frame. HIV and HCV infection characteristics, HCV potential exposures and sexual behaviour were collected by the physicians and via self-administered questionnaires. Phylogenetic analysis of the HCV-NS5B region was conducted. HCV incidence was 48/10 000 [95% Confidence Interval (CI):43-54] and 36/10 000 [95% CI: 30-42] in 2006 and 2007, respectively. Among the 80 men enrolled (median age: 40 years), 55% were HIV-diagnosed before 2000, 56% had at least one sexually transmitted infection in the year before HCV diagnosis; 55% were HCV-infected with genotype 4 (15 men in one 4d-cluster), 32.5% with genotype 1 (three 1a-clusters); five men were HCV re-infected; in the six-month preceding HCV diagnosis, 92% reported having casual sexual partners sought online (75.5%) and at sex venues (79%), unprotected anal sex (90%) and fisting (65%); using recreational drugs (62%) and bleeding during sex (55%). CONCLUSIONS: This study emphasizes the role of multiple unprotected sexual practices and recreational drugs use during sex in the HCV emergence in HIV-infected MSM. It becomes essential to adapt prevention strategies and inform HIV-infected MSM with recent acute HCV infection on risk of re-infection and on risk-reduction strategies

Occurrence of genes of putative fibrinogen binding proteins and hemolysins, as well as of their phenotypic correlates in isolates of S. lugdunensis of different origins

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus lugdunensis </it>is an important human pathogen that causes potentially fatal endocarditis, osteomyelitis and skin and soft tissue infections similar to diseases caused by <it>Staphylococcus aureus</it>. Nevertheless, in contrast to <it>S. aureus</it>, data on pathogenicity factors of <it>S. lugdunensis </it>is scarce. Two adhesins, a fibrinogen and a von Willebrand factor binding protein, and a <it>S. lugdunensis </it>synergistic hemolysin (SLUSH) have been previously described. Moreover, the newly sequenced genome of <it>S. lugdunensis </it>revealed genes of other putative fibrinogen binding adhesins and hemolysins. The aim of this study was to gain more insight into the occurrence of genes likely coding for fibrinogen binding adhesins and hemolysins using clinical strains of <it>S. lugdunensis</it>.</p> <p>Findings</p> <p>Most of the putative adhesin genes and hemolysin genes investigated in this study were highly prevalent, except for the SLUSH gene cluster. In contrast to previous reports, binding to fibrinogen was detected in 29.3% of the <it>S. lugdunensis </it>strains. In most strains, hemolysis on blood agar plates was weak after 24 h and distinct after 48 h of incubation. The fibrinogen binding and hemolysis phenotypes were also independent of the type of clinical specimen, from which the isolates were obtained.</p> <p>Conclusion</p> <p>In this study we described a pyrrolidonyl arylamidase negative <it>S. lugdunensis </it>isolate. Our data indicate that a matrix-assisted laser desorption ionisation time-of-flight MS-based identification of <it>S. lugdunensis </it>or species-specific PCR's should be performed in favour of pyrrolidonyl arylamidase testing. In contrast to the high occurrence of putative fibrinogen binding protein genes, 29.3% of the <it>S. lugdunensis </it>strains bound to fibrinogen. Putative hemolysin genes were also prevalent in most of the <it>S. lugdunensis </it>strains, irrespective of their hemolysis activity on Columbia blood agar plates. Similar to a previous report, hemolysis after 48 h of incubation is also indicative for <it>S. lugdunensis</it>. The SLUSH gene cluster was detected in an estimated 50% of the strains, indicating that this locus is different or non-prevalent in many strains.</p

pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia?

<p>Abstract</p> <p>Background</p> <p>The present study was conducted to analyze the value of ([¹⁸F] fluoromisonidazole (FMISO) and [¹⁸F]-2-fluoro-2'-deoxyglucose (FDG) PET as well as color pixel density (CPD) and tumor perfusion (TP) assessed by color duplex sonography (CDS) for determination of therapeutic relevant hypoxia. As a standard for measuring tissue oxygenation in human tumors, the invasive, computerized polarographic needle electrode system (pO₂histography) was used for comparing the different non invasive measurements.</p> <p>Methods</p> <p>Until now a total of 38 Patients with malignancies of the head and neck were examined. Tumor tissue pO₂was measured using a pO₂-histograph. The needle electrode was placed CT-controlled in the tumor without general or local anesthesia. To assess the biological and clinical relevance of oxygenation measurement, the relative frequency of pO₂readings, with values ≤ 2.5, ≤ 5.0 and ≤ 10.0 mmHg, as well as mean and median pO₂were stated. FMISO PET consisted of one static scan of the relevant region, performed 120 min after intravenous administration. FMISO tumor to muscle ratios (FMISO_T/M) and tumor to blood ratios (FMISO_T/B) were calculated. FDG PET of the lymph node metastases was performed 71 ± 17 min after intravenous administration. To visualize as many vessels as possible by CDS, a contrast enhancer (Levovist^®, Schering Corp., Germany) was administered. Color pixel density (CPD) was defined as the ratio of colored to grey pixels in a region of interest. From CDS signals two parameters were extracted: color hue – defining velocity (v) and color area – defining perfused area (A). Signal intensity as a measure of tissue perfusion (TP) was quantified as follows: TP = v_mean× A_mean.</p> <p>Results</p> <p>In order to investigate the degree of linear association, we calculated the Pearson correlation coefficient. Slight (|r| > 0.4) to moderate (|r| > 0.6) correlation was found between the parameters of pO₂polarography (pO₂readings with values ≤ 2.5, ≤ 5.0 and ≤ 10.0 mmHg, as well as median pO₂), CPD and FMISO_T/M. Only a slight correlation between TP and the fraction of pO₂values ≤ 10.0 mmHg, median and mean pO₂could be detected. After exclusion of four outliers the absolute values of the Pearson correlation coefficients increased clearly. There was no relevant association between mean or maximum FDG uptake and the different polarographic- as well as the CDS parameters.</p> <p>Conclusion</p> <p>CDS and FMISO PET represent different approaches for estimation of therapy relevant tumor hypoxia. Each of these approaches is methodologically limited, making evaluation of clinical potential in prospective studies necessary.</p

Fast relapse and high drop out rate of 48 weeks daily interferon monotherapy in HIV-infected patients with chronic hepatitis C

BACKGROUND: The standard of care for HCV Hepatitis is the combination of interferon (IFN) plus Ribavirin. In HIV patients the use of this combination therapy may induce drug interactions, and reduces the adherence to HAART. The aim of this study is to evaluate safety and efficacy of a 48 weeks daily dose IFN schedule. METHODS: We evaluated 50 coinfected patients; alpha IFN 2a was administered at a dose of 3 MU daily. The baseline values were the following : CD4+ 515 cells/mmc (mean); HIV-RNA <50 copies/ml in all patients; HCV-RNA 28, 3 × 106 copies/ml. RESULTS: At 48 weeks, 10 patients (20%) achieved a biochemical and virological response according to an intention to treat analysis. Twenty four patients (48%) underwent a drop-out mainly by side effects related to overlapping toxicity of interferon and antiretroviral therapy. All the patients, who responded to the treatment, showed a fast relapse one month after the end of treatment. CONCLUSION: Although our results demonstrated a very poor outcome and a bad tolerance to interferon monotherapy, this approach should not be dropped out, mainly in patients at high risk for side effects and in those with cirrhosis who do not tolerate or are at increased risk for the use of ribavirin